Project Summary/Abstract . The overall goal of the Strategies to Innovate Emergency Care Clinical Trials Network (SIREN) is to improve the outcome of patients suffering acute illness and injury by identifying effective treatments given in the earliest stages of care. Emergency conditions such as myocardial infarction, cardiac arrest, traumatic injury including brain and spinal cord injury, and seizures cause significant morbidity and mortality and exact a high cost in terms of human suffering and health care spending. Preclinical and translational research has demonstrated that there is a very narrow window of opportunity in which novel treatments for emergency conditions are optimally effective, and that conducting research in the emergency setting presents unique pragmatic challenges to clinical investigators. Effective clinical trials in these conditions require a coordinated network of emergency physicians, surgeons, cardiologists, intensivists, neurologists and biostatisticians. This proposal, in response to RFANS16014 describes the features, functions and coordination we will provide as the Clinical Coordinating Center for the SIREN network. The key elements of this structure will include an interdisciplinary team of investigators with specific expertise in the conduct of clinical trials of emergency interventions, a hubandspoke network design that acknowledges the importance of enrolling patients in the acute setting, and a long term network commitment to advancing the national research infrastructure as it relates to the interdisciplinary study of acute illness and injury. This project aims to create a coherent, collaborative, multidisciplinary emergency clinical trials community that is diverse and inclusive. The network will recruit, efficiently perform, and widely disseminate the most scientifically and clinically important trials necessary to advance the emergency care of patients with neurologic, cardiac, respiratory, hematologic and trauma emergencies. At least 4 large, simple trials in the ED and prehospital setting over the 5 year grant period will be initiated. The network aims to transform the emergency research enterprise, by exploring innovations in clinical trial designs (including adaptive and registrybased methods), by better and earlier engagement of patient stakeholders in trial planning, and by creative improvements in implementing and performing trials.